乙型肝炎病毒前基因组RNA存在于病毒粒子在等离子和关联有

StephenW

Hepatitis B Virus Pregenomic RNA Is Present in Virions in Plasma and Is Associated With a Response to Pegylated Interferon Alfa-2a and Nucleos(t)ide Analogues

    L. Jansen1,2, Neeltje A. Kootstra2, Karel A. van Dort2, R. Bart Takkenberg1, Hendrik W. Reesink1,2 and Hans L. Zaaijer3

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Author Affiliations

    1Department of Gastroenterology and Hepatology
    2Department of Experimental Immunology
    3Department of Clinical Virology, Academic Medical Center, University of Amsterdam, The Netherlands

    Correspondence: L. Jansen, MD, Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands ([email protected]).

    Presented in part: Liver Meeting, Washington, D. C., 4 November 2013. Abstract 1079; International Liver Congress, London, United Kingdom, 10 April 2014. Abstracts 182 and 684.

Abstract

Background. Treatment of patients with chronic hepatitis B (CHB) with nucleos(t)ide analogues (NAs) suppresses hepatitis B virus (HBV) DNA production but does not affect the synthesis of the RNA pregenome or HBV messenger RNA. Whether HBV RNA–containing particles continue to be secreted into the bloodstream remains controversial.

Methods. We developed a sensitive polymerase chain reaction (PCR) assay to quantify the HBV RNA load in a supernatant of NA-treated HepG2-2.2.15 cells and in plasma specimens from 20 patients with CHB who were receiving NA therapy and 86 patients treated with pegylated interferon alfa (Peg-IFN) and adefovir.

Results. Treatment of HepG2-2.2.15 cells with NAs for 9 days reduced HBV DNA levels (by 1.98 log10 copies/mL), whereas HBV RNA levels increased (by 0.47 log10 copies/mL; P < .05). During long-term NA treatment of patients with CHB, HBV RNA levels remained higher than HBV DNA levels. Peg-IFN–based treatment induced a stronger decrease in the HBV RNA load than NA monotherapy, and this decline was more pronounced in responders than in nonresponders. In HBV e antigen–negative patients, a lower baseline plasma HBV RNA level was independently associated with response to Peg-IFN and adefovir (odds ratio, 0.44; P = .019). Immunoprecipitation with HBV core antigen–specific antibodies after removal of the HBV surface antigen envelope demonstrated the association of plasma HBV RNA with virions.

Conclusions. HBV RNA is present in virions in plasma specimens from patients with CHB. HBV RNA levels vary significantly from those of established viral markers during antiviral treatment, which highlights its potential as an independent marker in the evaluation of patients with CHB.
Key words

    chronic hepatitis B HBV life cycle nucleocapsids immunoprecipitation response marker

    Received March 4, 2015.
    Accepted July 20, 2015.

    © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: [email protected].

StephenW

乙型肝炎病毒前基因组RNA存在于病毒粒子在等离子和关联有了回应聚乙二醇化干扰素α-2a和核苷（酸）类似物

    L. Jansen1,2，去往Neeltje A. Kootstra2，卡雷尔A.面包车Dort2，R.巴特Takkenberg1，亨德里克·W·Reesink1,2和Hans L. Zaaijer3

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作者机构

    胃肠病学和肝病学教研室
    实验免疫学教研室
    阿姆斯特丹大学3Department临床病毒学杂志，学术医学中心，荷兰

    函授：L.詹森博士，学和免疫学系，学术医学中心，阿姆斯特丹大学，Meibergdreef 9 1105 AZ阿姆斯特丹，荷兰（[email protected]）。

    提出部分：肝会议，华盛顿特区，11月4日2013年摘要1079;国际肝病会议上，英国伦敦，4月10日2014年文摘182和684。

抽象的

背景。慢性乙型肝炎（CHB）与核苷（酸）类似物（NAS）治疗抑制乙型肝炎病毒（HBV）DNA的生产，但不影响所述RNA前基因组或HBV信使RNA的合成。是否HBV RNA的含颗粒继续被分泌到血液中仍存在争议。

方法。我们开发了一种敏感聚合酶链反应（PCR）测定法来定量乙肝病毒的RNA负载在NA处理HepG2-2.2.15细胞的上清液，并在20 CHB患者正在接受谁NA疗法和86例血浆标本PEG化处理干扰素α（PEG-IFN）和阿德福韦。

结果。 HepG2-2.2.15细胞治疗使用NAS 9天减少HBV DNA水平（由1.98 log10拷贝/毫升），而HBV RNA水平增加（由0.47 log10拷贝/毫升; P <0.05）。在长期NA治疗的慢性乙肝患者，乙肝病毒RNA水平仍高于HBV DNA水平较高。聚乙二醇干扰素为基础的治疗引起的HBV RNA负荷比NA单一更强的下降，而这种下降是比无反应者更加明显的反应。在乙肝病毒e抗原阴性患者，一个较低的基线血浆乙肝病毒RNA水平是独立与响应聚乙二醇干扰素和阿德福韦（; P = 0.019比值比为0.44）有关。免疫沉淀并除去HBV表面抗原信封的后HBV核心抗原特异性抗体证明了等离子体的HBV的RNA与病毒体的关联。

结论。乙肝病毒的RNA存在于从慢性乙型肝炎患者的血浆样品的病毒粒子。 HBV的RNA水平期间抗病毒治疗，这强调了其潜在如在慢性乙型肝炎患者的评价提供独立的标记物变化显著从那些成立病毒标记物。
关键词

    慢性乙肝HBV生命周期核衣壳免疫反应标记

    收到2015年3月4日。
    接受二零一五年七月二十零日。

    ©该作者2015年出版由牛津大学出版社代表的美国传染病学会的。版权所有。对于权限，请电邮：[email protected]。